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Abstract Osteoarthritis (OA) is a degenerative joint disease mostly occurring in the knee. Bone marrow- derived mesenchymal stem cells are multipotent stromal cells that can provide a promising treatment in tissue regeneration. Intra-articular injection of Hyaluronic acid (HA) has been widely used for treatment of knee OA. Bee venom (BV) treatment as an oriental medicine has been used for many years to treat inflammatory diseases such as arthritis. The purpose of this study was to compare the therapeutic effect of mesenchymal stem cells (MSCs), (HA) and (BV) Sixty albino rats were divided into six groups. group (1) served as control, groups (2,3,4,5,6) served as arthritic rats and given single intra-articular injection of 1 mg of monosodium iodoacetate. group 3 is injected with a single dose of 2 x 106 stem cell (intraarticularly) while group 4 is treated with the same dose but interaperteonialy and group 5 is treated with a therapeutic dose of (HA). group 6 is injected subcutaneously with (0.1 ml/1ml) with (BV). Radiological, biochemical histopathological and histochemical analysis were performed before and after treatment. Biochemically there were highly significant decrease in C-reactive protein, Rhematoid factor Alkaline phosphatase and osteocalcin after treatment. Radiological, histopathological and histochemical results showed marked improvement in MSCs treated group, The animals injected with HA revealed less degree of improvement compared to animals treated with stem cells. After treatment with BV mild to moderate improvement was recorded in joint compared to previous groups. MSCs is an effective option for treating OA |